Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I

Department of Pediatrics, Saint Louis University, St Louis, MO 63104, USA.
Journal of Inherited Metabolic Disease (Impact Factor: 3.37). 02/2010; 33(2):141-50. DOI: 10.1007/s10545-009-9036-3
Source: PubMed


Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by deficiency of alpha-L-iduronidase leading to accumulation of its catabolic substrates, dermatan sulfate (DS) and heparan sulfate (HS), in lysosomes. This results in progressive multiorgan dysfunction and death in early childhood. The recent success of enzyme replacement therapy (ERT) for MPS I highlights the need for biomarkers that reflect response to such therapy. To determine which biochemical markers are better, we determined serum and urine DS and HS levels by liquid chromatography tandem mass spectrometry in ERT-treated MPS I patients. The group included one Hurler, 11 Hurler/Scheie, and two Scheie patients. Seven patients were treated from week 1, whereas the other seven were treated from week 26. Serum and urine DS (DeltaDi-4S/6S) and HS (DeltaDiHS-0S, DeltaDiHS-NS) were measured at baseline, week 26, and week 72. Serum DeltaDi-4S/6S, DeltaDiHS-0S, and DeltaDiHS-NS levels decreased by 72%, 56%, and 56%, respectively, from baseline at week 72. Urinary glycosaminoglycan level decreased by 61.2%, whereas urine DeltaDi-4S/6S, DeltaDiHS-0S, and DeltaDiHS-NS decreased by 66.8%, 71.8%, and 71%, respectively. Regardless of age and clinical severity, all patients showed marked decrease of DS and HS in blood and urine samples. We also evaluated serum DS and HS from dried blood-spot samples of three MPS I newborn patients, showing marked elevation of DS and HS levels compared with those in control newborns. In conclusion, blood and urine levels of DS and HS provide an intrinsic monitoring and screening tool for MPS I patients.

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    • "We and others have developed new methods to assay CS, DS, HS, and KS simultaneously in the blood, urine, and/or DBS samples by using liquid chromatography tandem mass spectrometry (LC– MS/MS) [7,14–23]. The LC–MS/MS method not only shows sensitivity and specificity for detecting all subtypes of MPS, but also monitors therapeutic efficacy in MPS patients and animal models [1] [16] [22] [24] [25]; however, since LC processing is time consuming, the main drawback of this method is throughput. This factor may limit its utility for assaying large numbers of samples. "
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    ABSTRACT: Mucopolysaccharidoses (MPS) are caused by deficiency of one of a group of specific lysosomal enzymes, resulting in excessive accumulation of glycosaminoglycans (GAGs). We previously developed GAG assay methods using liquid chromatography tandem mass spectrometry (LC-MS/MS); however, it takes 4-5 min per sample for analysis. For the large numbers of samples in a screening program, a more rapid process is desirable. The automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) integrates a solid phase extraction robot to concentrate and desalt samples prior to direction into the MS/MS without chromatographic separation; thereby allowing each sample to be processed within 10 s (enabling screening of more than one million samples per year). The aim of this study was to develop a higher throughput system to assay heparan sulfate (HS) using HT-MS/MS, and to compare its reproducibility, sensitivity and specificity with conventional LC-MS/MS.
    Full-text · Article · Sep 2014 · Molecular Genetics and Metabolism
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    • "Some of the features of an ideal BM include the simple and rapid assessment in easily accessible tissues and body fluids, the ideal reflection of total body burden of the disease, the narrow range in the variation of the BM concentration or activity in the general population and the absence of overlap between the quantity of the analyte in naive patients and healthy subjects [4]. Apart from the identification and common employment of plasma chitotriosidase as a first screen in Gaucher disease [6], there are currently very few BMs in LSDs, of which even fewer are engaged in clinical use [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]. The extracellular matrix (ECM) represents an intricate network of macromolecules whose components represent research targets concerning BM discovery in numerous pathologic conditions. "
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